Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil

NCT03399604 | Completed Phase 3 Results FDA Drug

• 1 other identifier: LTI-301
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 38

Brief Summary

The primary objective of this study is to evaluate the long-term safety and tolerability of LIQ861, a dry powder formulation of treprostinil, in patients with Pulmonary Arterial Hypertension (PAH).

Conditions

Primary Pulmonary Hypertension

Keywords

Pulmonary Arterial Hypertension; Idiopathic Pulmonary Arterial Hypertension; Heritable Pulmonary Arterial Hypertension; Drug Induced Pulmonary Arterial Hypertension; Toxin Induced Pulmonary Arterial Hypertension; Connective tissue disease

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

  There were two treatment arms analyzed for events in the study. All subjects that participated in the PK study were part of the transition group and not analyzed separately for adverse events. Treatment-Emergent Adverse Events and Serious Adverse Events will be grouped by MedDRA System Organ Class, dose level, time on drug, and relationship to dose titration

  Baseline, Week 2, Month 1, Month 2 Visits, with bimonthly follow up for up to 16 months.

Study Arms (1)

LIQ861 Inhaled Treprostinil

EXPERIMENTAL

LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg. LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.

Drug: LIQ861 Inhaled Treprostinil

Interventions

LIQ861 Inhaled Treprostinil DRUG

LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg treprostinil.

Also known as: inhaled treprostinil, inhaled prostacyclin

LIQ861 Inhaled Treprostinil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• signed informed consent by patient prior to study enrollment
• years of age or older
• If female of childbearing potential, a negative pregnancy test at the Baseline Visit and agrees to practice adequate birth control throughout the duration of the study. If the patient is postmenopausal or has documented surgical sterilization, a pregnancy test and birth control is not necessary.
• The patient has been diagnosed with PAH belonging to the following subgroups of the updated Nice Clinical Classification Group 1 (Simonneau, Gatzoulis et al. 2013), which include:
• Idiopathic PAH (1.1), or
• Heritable PAH (1.2), or
• Drug and toxin induced PAH (1.3), or
• PAH associated with connective tissue disease (1.4.1), HIV infection (1.4.2), or congenital heart disease (1.4.4) with simple systemic-to-pulmonary shunt at least 1 year after surgical repair
• The patient has been diagnosed with PAH and is NYHA Functional Class II - IV at Screening.
• has documented stable doses of approved inhaled therapy for at least 3 months prior to screening and is willing and able to transition from their prescribed dose of inhaled therapy to study drug, or
• has documented stable doses of no more than two approved oral therapies for at least 3 months prior to screening and is willing and able to add LIQ861 to their treatment regimen.
• The patient can complete a baseline six-minute walk distance (6MWD) ≥ 150 m.
• The patient has had evidence of FEV1 ≥ 60% and FEV1/FVC ratio ≥ 60% during the 6-month period prior to enrollment.

You may not qualify if:

• The patient's clinical condition is such that, in the opinion of the Investigator, they are not expected to remain clinically stable for the duration of the study.
• The patient is currently taking oral prostacyclin analogues or agonists, including treprostinil and selexipag.
• The patient has had any PAH medication (except for anticoagulants) discontinued within 14 days of Baseline.
• The patient has had a new type of chronic therapy (including but not limited to oxygen, a different class of vasodilator, diuretic, digoxin, and digitalis) for pulmonary hypertension added within 30 days of Baseline.
• The patient has uncontrolled systemic hypertension as evidenced by persistent systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
• The patient has a history of hemodynamically significant left-sided heart disease including, but not limited to: aortic or mitral valve disease, pericardial constriction, restrictive or congestive cardiomyopathy, or coronary artery disease (CAD).
• The patient has had an atrial septostomy.
• The patient has any serious or life-threatening disease other than conditions associated with PAH (e.g. malignancy requiring aggressive chemotherapy, end stage renal disease, etc.).
• The patient is taking any excluded medications listed in the Investigator's Brochure, namely inhibitors and inducers of CYP2C8
• The patient has a hypersensitivity or allergy to any of the ingredients of LIQ861 or other clinically relevant allergies (clinical relevance per Investigator judgment).
• The patient has had a pulmonary infarction (defined as infarction in more than one lung segment documented by V/Q scan or pulmonary angiography) within two weeks of Screening.
• The patient has had a stroke or transient ischemic attack (TIA) within six months of Screening.
• The patient has evidence of an active uncontrolled sepsis or systemic infection during Screening.
• The patient is pregnant or lactating.
• The patient has any musculoskeletal disease or any other disease that would limit ambulation.

Sponsors & Collaborators

• Liquidia Technologies, Inc.: lead
• Nuventra, Inc.: collaborator

Study Sites (38)

Banner University Medical Center

Phoenix, Arizona, 85006, United States

Location

Arizona Pulmonary Specialists, Ltd.

Phoenix, Arizona, 85012, United States

Location

West Los Angeles VA Healthcare Center

Los Angeles, California, 90073, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Los Angeles Biomedical Research Center

Torrance, California, 90502, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

AdventHealth

Orlando, Florida, 32803, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Wellstar Research Institute

Marietta, Georgia, 30060, United States

Location

Northwestern Medicine, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

Location

Kentuckiana Pulmonary Research Center

Louisville, Kentucky, 40202, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55435, United States

Location

Mayo Clinic-Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of New Mexico Health Science Center

Albuquerque, New Mexico, 87106, United States

Location

NYU Winthrop University Hospital

Mineola, New York, 11501, United States

Location

NYU Langone Health

New York, New York, 10279, United States

Location

University of North Carolina School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

University Hospitals of Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

the Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science Center

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Alleghany General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Lung Center

Houston, Texas, 77030, United States

Location

University of Texas - Health Science Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

INOVA Fairfax Medical Campus

Falls Church, Virginia, 22042, United States

Location

The Medical College of Wisconsin/Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Roscigno R, Vaughn T, Anderson S, Wargin W, Hunt T, Hill NS. Pharmacokinetics and tolerability of LIQ861, a novel dry-powder formulation of treprostinil. Pulm Circ. 2020 Nov 19;10(4):2045894020971509. doi: 10.1177/2045894020971509. eCollection 2020 Oct-Dec.

  PMID: 33282202 DERIVED

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension; Pulmonary Arterial Hypertension; Connective Tissue Diseases

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Chief Medical Offier
• Organization: Liquidia Technologies

safety@liquidia.com

919-328-4400

Study Officials

• Nicholas S Hill, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will evaluate the long term safety and tolerability of LIQ861 in PAH patients transitioning from stable doses of inhaled treprostinil therapy, or who are taking no more than 2 approved, non-prostacylcin, oral PAH therapies. Patients transitioning from inhaled treprostinil will be initiated at a comparable dose of LIQ861, and then titrate in 25ug incremental doses to tolerance and symptom relief. Patients adding LIQ861 to current oral therapies will start at a 25ug dose, and increase in 25ug increments on a weekly basis to tolerance and symptom relief. A subset of the patients transitioning from inhaled treprostinil will be enrolled in a one-directional crossover to compare the bioavailability and pharmacokinetics of treprostinil as they transition to LIQ861. Serial PK sample collections will be taken on back to back days for transitioning and LIQ861 treprostinil formulations. These patients will then continue to be followed as all other patients enrolled in the study.

Study Record Dates

• First Submitted: January 3, 2018
• First Posted: January 16, 2018
• Study Start: January 2, 2018
• Primary Completion: May 6, 2019
• Study Completion: November 25, 2019
• Last Updated: July 30, 2024
• Results First Posted: July 30, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (38)